crossing96/oncoscreening huggingface dataset:
Rosiglitazone and trametinib exhibit potent anti-tumor activity in a mouse model of muscle invasive bladder cancer.	Muscle invasive bladder cancers (BCs) can be divided into 2 major subgroups-basal/squamous (BASQ) tumors and luminal tumors. Since Pparg has low or undetectable expression in BASQ tumors, we tested the effects of rosiglitazone, Pparg agonist, in a mouse model of BASQ BC. We find that rosiglitazone reduces proliferation while treatment with rosiglitazone plus trametinib, a MEK inhibitor, induces apoptosis and reduces tumor volume by 91% after 1 month. Rosiglitazone and trametinib also induce a shift from BASQ to luminal differentiation in tumors, which our analysis suggests is mediated by retinoid signaling, a pathway known to drive the luminal differentiation program. Our data suggest that rosiglitazone, trametinib, and retinoids, which are all FDA approved, may be clinically active in BASQ tumors in patients.	bladder
Location-specific diagnostic efficiency of photodynamic diagnosis-guided biopsy in bladder mapping biopsies.	BACKGROUND: Photodynamic diagnosis (PDD)-assisted transurethral resection of bladder tumors (TURBT) has emerged as a promising complementary tool to white light (WL) cystoscopy, potentially improving cancer detection and replacing conventional mapping biopsies. This study aimed to investigate the diagnostic accuracy of PDD by anatomical locations in mapping biopsies through lesion-based analysis. METHODS: PDD and WL findings were prospectively recorded in 102 patients undergoing mapping biopsies and PDD-assisted TURBT using oral 5-aminolevulinic acid. We evaluated 673 specimens collected from flat tumor or normal-looking lesions on WL cystoscopy, after excluding 98 specimens collected from papillary or nodular tumors. RESULTS: Among the 673 lesions, cancer was detected in 110 (16%) by lesion-based analysis. PDD demonstrated significantly higher sensitivity (65.5% vs. 46.4%, p < 0.001) and negative predictive value (92.5% vs. 89.5%, p < 0.001) compared to WL. The sensitivity of PDD findings varied by location: posterior (100%), right (78.6%), dome (73.3%), left (70.6%), trigone (58.8%), bladder neck (41.7%), anterior (40.0%), and prostatic urethra (25.0%). Incorporating targeted biopsies of specific locations (bladder neck, anterior, and prostatic urethra) into the PDD-guided biopsies, regardless of PDD findings, significantly increased the overall sensitivity from 65.5% to 82.7% (p = 0.001). CONCLUSIONS: This study first demonstrated the detection rate of location-specific mapping biopsies using PDD, revealing difficulties in accuracy assessment in areas susceptible to tangential fluorescence. While PDD-guided biopsy improves cancer detection compared to WL cystoscopy even for flat tumors or normal-looking lesions, more careful decisions, including mapping biopsies, may be beneficial for an assessment in these tangential areas.	bladder
Tumor necrosis in magnetic resonance imaging predicts urothelial carcinoma with squamous differentiation in muscle-invasive bladder carcinoma.	PURPOSE: This study investigated radiologic features on preoperative MRI to differentiate urothelial carcinoma with squamous differentiation (UCSD) from conventional urothelial carcinoma (UC) in muscle-invasive bladder carcinoma. METHODS: Ninety-nine patients who underwent radical cystectomy and a preoperative bladder MRI scan within three months before surgery were retrospectively enrolled. Various MRI features, including tumor length, location, multiplicity, long-to-short axis ratio, morphology, radiologic stage, and degree of severe necrosis, were analyzed. Univariable and multivariable logistic regression analyses were performed to identify MRI features predictive of UCSD. The diagnostic performance of a significant MRI feature was assessed using 5-fold cross-validation. RESULTS: Among the MRI features, significant radiologic findings associated with UCSD in the univariable analysis included heterogeneous tumor signal intensity in T2-weighted images (odds ratio [OR], 3.365; 95% confidence interval [CI], 1.213-9.986; P = 0.022) and contrast-enhanced T1-weighted images (OR, 4.428; 95% CI, 1.519-12.730; P = 0.007), as well as marked (≥ 50%) severe necrosis (OR, 17.100; 95% CI, 4.699-73.563; P < 0.001). In the multivariable analysis, marked (≥ 50%) severe necrosis (odds ratio [OR], 13.755; 95% confidence interval [CI], 2.796-89.118; P = 0.004) was a significant predictor of UCSD. Marked (≥ 50%) severe necrosis showed a high specificity of 95.0% with a precision of 65.0% for diagnosing UCSD based on 5-fold cross-validation. CONCLUSION: Preoperative bladder MRI revealing marked severe necrosis may be indicative of UCSD and can assist in distinguishing it from conventional UC.	bladder
CYP19A1 polymorphisms and bladder cancer risk in the Chinese Han population.	BACKGROUND: The expression of CYP19A1 has implications for the prognosis of female bladder cancer. However, this study aimed to explore the association between single nucleotide polymorphisms (SNPs) in CYP19A1 and bladder cancer risk, as no prior research has addressed this association. RESEARCH DESIGN AND METHODS: We selected and genotyped five CYP19A1 SNPs (rs4646, rs6493487, rs1062033, rs17601876, and rs3751599) in 217 patients and 550 controls using the Agena MassARRAY system. Logistic regression analysis was employed to calculate the odds ratio (OR) and 95% confidence intervals (CIs). Bioinformatics predicted SNP functions and CYP19A1 involving pathways. RESULTS: Our study revealed a significant association between bladder cancer risk and four SNPs (rs4646 (AC vs. CC: OR = 1.71, FDR-p = 0.005), rs6493487 (G vs. A: OR = 0.68, FDR-p = 0.011), rs1062033 (G vs. C: OR = 0.36, FDR-p < 0.001), and rs17601876 (GA vs. GG: OR = 1.66, FDR-p = 0.008)) in CYP19A1. The three SNPs (rs4646, rs1062033, and rs17601876) were significantly correlated with CYP19A1 expression levels in normal whole blood (p < 0.05). Moreover, CYP19A1 was found to primarily participate in the steroid hormone biosynthesis and metabolic pathways. CONCLUSIONS: Consequently, CYP19A1 gene polymorphisms may play a crucial role in the genetic susceptibility to bladder cancer.	bladder
Sulforaphane suppresses bladder cancer metastasis via blocking actin nucleation-mediated pseudopodia formation.	Metastasis is the primary stumbling block to the treatment of bladder cancer (BC). In order to spread, tumor cells must acquire increased migratory and invasive capacity, which is tightly linked with pseudopodia formation. Here, we unravel the effects of sulforaphane (SFN), an isothiocyanate in cruciferous vegetables, on the assembly of pseudopodia and BC metastasis, and its molecular mechanism in the process. Our database analysis revealed that in bladder tumor, pseudopodia-associated genes, CTTN, WASL and ACTR2/ARP2 are upregulated. SFN caused lamellipodia to collapse in BC cells by blocking the CTTN-ARP2 axis. SFN inhibited invadopodia formation and cell invasion by reducing WASL in different invasive BC cell lines. The production of ATP, essential for the assembly of pseudopodia, was significantly increased in bladder tumors and strongly inhibited by SFN. Overexpressing AKT1 reversed the downregulation of ATP in SFN-treated bladder cancer cells and restored filopodia and lamellipodia morphology and function. Bioluminescent imaging showed that SFN suppressed BC metastases to the lung of nude mice while downregulating Cttn and Arp2 expression. Our study thus reveals mechanisms of SFN action in inhibiting pseudopodia formation and highlights potential targeting options for the therapy of metastatic bladder cancer.	bladder
Prognostic role of the neutrophil/lymphocyte ratio in high-risk BCG-naïve non-muscle-invasive bladder cancer treated with intravesical gemcitabine/docetaxel.	OBJECTIVES: To investigate the role of pretreatment neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in the prediction of response to sequential intravesical therapy, gemcitabine and docetaxel (Gem/Doce), given to patients with bacille Calmette-Guérin (BCG)- naïve high-risk non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: A retrospective analysis was conducted on 115 patients who received intravesical Gem/Doce for high-risk NMIBC between January 2011 and December 2021. Data were computed as the median (interquartile range [IQR]) or mean (standard deviation [sd]). Cox regression analysis was performed to determine if neutrophilia, NLR, platelet counts, and PLR before instillation therapy were predictive of recurrence-free survival (RFS) and overall survival (OS). Predictive performance was estimated using Uno's C-statistic. RESULTS: The median (IQR) follow-up for the overall cohort was 23 (13-36) months. The mean (sd) values for NLR, PLR and platelet counts were 3.4 (2.3), 142.2 (85.5), and 225.2 (75.1) × 10(9)/L, respectively. NLR was associated with RFS, with a hazard ratio of 1.32 (95% confidence interval CI 1.19-1.46). Concordance analysis showed that NLR had a good ability to predict RFS (C-index: 0.7, P < 0.01). The PLR and platelet count were not associated with RFS and did not predict recurrence. In terms of OS, none of these cellular inflammatory markers showed any prediction value. CONCLUSION: Pre-treatment NLR provides some predictive accuracy for RFS in high-risk BCG-naïve patients receiving Gem/Doce. Further prospective trials are needed to validate this finding.	bladder
The Novel Platinum Analog Dicycloplatin Provides Reliable Growth Inhibition of Urothelial Carcinoma Cells In Vitro.	BACKGROUND/AIM: Platinum-based chemotherapies are a component of standard-of-care regimens for urothelial carcinoma (UC). These nephrotoxic drugs are often dose-limiting, with cisplatin and carboplatin being the most commonly used. Dicycloplatin (DCP) has better solubility and stability, with comparable efficacy and better tolerability. Some suggest the use of DCP as primary treatment for non-muscle-invasive bladder cancer. We exposed UC cell lines to DCP in vitro to assess its efficacy. MATERIALS AND METHODS: A high grade (IV) in vitro UC cell line (TCCSUP) was exposed to varying concentrations of cisplatin (0-600 μg/ml), carboplatin (0-600 μg/ml), oxaliplatin (0-4.0 μg/ml), and DCP (0-350 μg/ml). Grade II-IV cells were exposed to varying concentrations of DCP (0-350 μg/ml) to assess time- and concentration-dependent growth inhibition, and simulate intravesical treatment. Growth inhibition was determined following 24, 48, and 72 h of exposure, using a tetrazolium dye to assess mitochondrial dehydrogenase activity. RESULTS: DCP, cisplatin, and carboplatin effectively achieved >90% cell kill at 72 h. Concentrations of 325 μg/ml DCP, 50 μg/ml cisplatin, and 600 μg/ml carboplatin were sufficient for >90% cell-kill, with cisplatin demonstrating the highest efficacy at the lowest concentration/time intervals. Dose- and time-dependent cell kill were demonstrated at varying concentrations of DCP in grade II-IV cell lines, including cells exposed intravesically. CONCLUSION: In vitro, DCP demonstrates cell-killing efficacy in a time- and concentration-dependent manner in grade II-IV UC cell lines, showing promise for its intravenous, oral, and intravesical use for bladder UC in both primary and adjuvant/neoadjuvant settings.	bladder
Perioperative chemotherapy and immunotherapy to optimize cystectomy outcomes in the curative intent of non-metastatic muscle-invasive bladder cancer: A systematic review and meta-analysis.	INTRODUCTION: Perioperative systemic treatments play a crucial role in the comprehensive management of muscle-invasive bladder cancer. While neoadjuvant platinum-based chemotherapy has a proven efficacy, administering adjuvant chemotherapy can be challenging in patients with multiple comorbidities. Although immunotherapy has shown success in metastatic settings, its effectiveness in both neoadjuvant and adjuvant settings remains under investigation. This study aims to conduct a systematic literature review and meta-analysis to assess the impact of chemotherapy and/or immunotherapy in neoadjuvant and/or adjuvant settings. METHODS: A systematic review and meta-analysis were conducted by consulting the PubMed, Scopus, and ClinicalTrial.gov databases for the period from 1994 to 2023. The analysis utilized Forest Plots for key points of interest: overall survival/pathologic response for neoadjuvant chemotherapy (NAC) and overall survival/disease-free survival for adjuvant chemotherapy (AC), employing random or fixed models. RESULTS: The systematic review included 26 articles, and 14 were incorporated into the meta-analysis. For NAC, five studies assessed overall survival, yielding an overall hazard ratio (HR) of 0.84 [0.75-0.94]; P=0.002. Pathologic response under NAC was evaluated in five studies, resulting in an overall odds ratio (OR) of 0.3 [0.2-0.4]; P<0.001 compared to cystectomy and 0.86 [0.65-1.13]; P=0.28 for MVAC vs. GC. Regarding AC, six studies investigated overall survival, revealing an overall HR of 0.93 [0.77-1.12]; P=0.46. Disease-free survival under AC was examined in seven studies, with an overall OR of 0.58 [0.44-0.78]; P<0.001. Meta-analysis was not conducted for immunotherapy due to limited phase II studies in the neoadjuvant setting and only two available studies in the adjuvant setting. CONCLUSION: This study reaffirms the efficacy of platinum-based chemotherapy in neoadjuvant and adjuvant scenarios, enhancing overall survival in muscle-invasive bladder cancer patients. Immunotherapy exhibits promising outcomes in tumor downstaging in the neoadjuvant setting and in disease-free survival, in the adjuvant setting.	bladder
Role of (64)CuCl(2) PET/CT in Detecting and Staging Muscle-Invasive Bladder Cancer: Comparison with Contrast-Enhanced CT and (18)F-FDG PET/CT.	"Molecular imaging of muscle-invasive bladder cancer (MBC) is restricted to its locoregional and distant metastases, since most radiopharmaceuticals have a urinary excretion that limits the visualization of the primary tumor. (64)CuCl(2) (,) a positron-emitting radiotracer with nearly exclusive biliary elimination, could be well suited to exploring urinary tract neoplasms. In this study, we evaluated the feasibility of (64)CuCl(2)-based staging of patients with MBC; furthermore, we compared the diagnostic capability of this method with those of the current gold standards, that is, contrast-enhanced CT (ceCT) and (18)F-FDG PET/CT. Methods: We prospectively enrolled patients referred to our institution for pathology-confirmed MBC staging/restaging between September 2021 and January 2023. All patients underwent ceCT, (18)F-FDG, and (64)CuCl(2) PET/CT within 2 wk. Patient-based analysis and lesion-based analysis were performed for all of the potentially affected districts (overall, bladder wall, lymph nodes, skeleton, liver, lung, and pelvic soft tissue). Results: Forty-two patients (9 women) were enrolled. Thirty-six (86%) had evidence of disease, with a total of 353 disease sites. On patient-based analysis, ceCT and (64)CuCl(2) PET/CT showed higher sensitivity than (18)F-FDG PET/CT in detecting the primary tumor (P < 0.001); moreover, (64)CuCl(2) PET/CT was slightly more sensitive than (18)F-FDG PET/CT in disclosing soft-tissue lesions (P < 0.05). Both PET methods were more specific and accurate than ceCT in classifying nodal lesions (P < 0.05). On lesion-based analysis, (64)CuCl(2) PET/CT outperformed (18)F-FDG PET/CT and ceCT in detecting disease localizations overall (P < 0.001), in the lymph nodes (P < 0.01), in the skeleton (P < 0.001), and in the soft tissue (P < 0.05). Conclusion: (64)CuCl(2) PET/CT appears to be a sensitive modality for staging/restaging of MBC and might represent a ""one-stop shop"" diagnostic method in these scenarios."	bladder
Comprehending the pharmacological mechanism of marine phenolic acids in bladder cancer therapy against matrix metalloproteinase 9 protein by integrated network pharmacology and in-silico approaches.	Bladder cancer (BC) is the 10th most common tumour with a high incidence and recurrence rate worldwide; however, the current therapies present limitations as, regularly, not all patients benefit from treatment. Therefore, the search for new, active marine phenolic acids with anti-tumour properties is imperative. In this study, we subjected marine phenolic acids to in silico investigations such as network pharmacology, molecular docking, and molecular dynamics simulation (MD) to identify a plausible pathway and the lead compound that inhibits BC. According to the network pharmacology analysis, eight hub genes (PLAU, MMP2, ITGB3, MAPK1, PTPN11, ESR1, TLR4, MMP9) were found and linked to the enrichment of hsa05205: proteoglycans in cancer, and four hub genes (MMP1, MMP2, MAPK1, MMP9) were involved in the enrichment of hsa05219: BC. Subsequently, molecular docking studies showed that the marine phenolic acids exhibit a strong binding affinity for the target protein, matrix metalloproteinase-9 (MPP9). Among these 14 marine phenolic acids, chicoric acid showed the highest binding affinity of -67.1445 kcal/mol and formed hydrogen bonds with the residues of Ala189, Gln227, Leu188, His226, Ala242, Arg249, Ala191, and Gly186 in the active site of the MPP9 protein. Then, molecular dynamics simulation revealed that chicoric acid formed a stable protein-ligand complex with RMSD and RMSF values of 0.72 nm and 0.53 nm, respectively. Furthermore, the PCA method was employed to understand the dynamical behaviour in the conformational space of MPP9 protein bound to chicoric acid, and the results showed the good conformational space behaviour of MPP9 protein. Moreover, chicoric acid showed a free binding energy value of -32.62 kcal/mol, which indicated it could be a BC inhibitor. Overall, chicoric acid demonstrated potential anti-BC activity through MPP9 protein inhibition.	bladder
m6A-Mediated Induction of 7-Dehydrocholesterol Reductase Stimulates Cholesterol Synthesis and cAMP Signaling to Promote Bladder Cancer Metastasis.	Dysregulation of cholesterol homeostasis occurs in multiple types of tumors and promotes cancer progression. Investigating the specific processes that induce abnormal cholesterol metabolism could identify therapeutic targets to improve cancer treatment. In this investigation, we observed upregulation of 7-dehydrocholesterol reductase (DHCR7), a vital enzyme involved in the synthesis of cholesterol, within bladder cancer tissues in comparison to normal tissues, which was correlated with increased bladder cancer metastasis. Increased expression of DHCR7 in bladder cancer was attributed to decreased mRNA degradation mediated by YTHDF2. Loss or inhibition of DHCR7 reduced bladder cancer cell invasion in vitro and metastasis in vivo. Mechanistically, DHCR7 promoted bladder cancer metastasis by activating the cAMP/protein kinase A/FAK pathway. Specifically, DHCR7 increased cAMP levels by elevating cholesterol content in lipid rafts, thereby facilitating the transduction of signaling pathways mediated by cAMP receptors. DHCR7 additionally enhanced the cAMP signaling pathway by reducing the concentration of 7-dehydrocholesterol and promoting the transcription of the G protein-coupled receptor, namely gastric inhibitory polypeptide receptor. Overall, these findings demonstrate that DHCR7 plays an important role in bladder cancer invasion and metastasis by modulating cholesterol synthesis and cAMP signaling. Furthermore, inhibition of DHCR7 shows promise as a viable therapeutic strategy for suppressing bladder cancer invasion and metastasis. Significance: Inhibiting DHCR7 induces cholesterol metabolism reprogramming and lipid raft remodeling to inactivate the cAMP/protein kinase A/FAK axis and suppress bladder cancer metastasis, indicating the therapeutic potential of targeting DHCR7.	bladder
circHIPK3 nucleates IGF2BP2 and functions as a competing endogenous RNA.	Circular RNAs represent a class of endogenous RNAs that regulate gene expression and influence cell biological decisions with implications for the pathogenesis of several diseases. Here, we disclose a novel gene-regulatory role of circHIPK3 by combining analyses of large genomics datasets and mechanistic cell biological follow-up experiments. Using time-course depletion of circHIPK3 and specific candidate RNA-binding proteins, we identify several perturbed genes by RNA sequencing analyses. Expression-coupled motif analyses identify an 11-mer motif within circHIPK3, which also becomes enriched in genes that are downregulated upon circHIPK3 depletion. By mining eCLIP datasets and combined with RNA immunoprecipitation assays, we demonstrate that the 11-mer motif constitutes a strong binding site for IGF2BP2 in bladder cancer cell lines. Our results suggest that circHIPK3 can sequester IGF2BP2 as a competing endogenous RNA (ceRNA), leading to target mRNA stabilization. As an example of a circHIPK3-regulated gene, we focus on the STAT3 mRNA as a specific substrate of IGF2BP2 and validate that manipulation of circHIPK3 regulates IGF2BP2-STAT3 mRNA binding and, thereby, STAT3 mRNA levels. Surprisingly, absolute copy number quantifications demonstrate that IGF2BP2 outnumbers circHIPK3 by orders of magnitude, which is inconsistent with a simple 1:1 ceRNA hypothesis. Instead, we show that circHIPK3 can nucleate multiple copies of IGF2BP2, potentially via phase separation, to produce IGF2BP2 condensates. Our results support a model where a few cellular circHIPK3 molecules can induce IGF2BP2 condensation, thereby regulating key factors for cell proliferation.	bladder
Association between CYP1A2 gene variants -163 C/A (rs762551) and -3860 G/A (rs2069514) and bladder cancer susceptibility.	BACKGROUND: Bladder cancer (BLCA) poses a significant global health challenge due to its high incidence, poor prognosis, and limited treatment options. AIMS AND OBJECTIVES: This study aims to investigate the association between two specific polymorphisms, CYP1A2-163 C/A and CYP1A2-3860G/A, within the Cytochrome P450 1A2 (CYP1A2) gene and susceptibility to BLCA. METHODS: The study employed a case-control design, genotyping 340 individuals using Polymerase Chain Reaction-High-Resolution Melting Curve (PCR-HRM). Various genetic models were applied to evaluate allele and genotype frequencies. Genetic linkage analysis was facilitated using R packages. RESULTS: The study reveals a significant association with the - 163 C/A allele, particularly in the additive model. Odds ratio (OR) analysis links CYP1A2-163 C/A (rs762551) and CYP1A2-3860G/A(rs2069514) polymorphisms to BLCA susceptibility. The rs762551 C/A genotype is prevalent in 55% of BLCA cases and exhibits an OR of 2.21. The A/A genotype has an OR of 1.54. Regarding CYP1A2-3860G/A, the G/A genotype has an OR of 1.54, and the A/A genotype has an OR of 2.08. Haplotype analysis shows a predominant C-C haplotype at 38.2%, followed by a C-A haplotype at 54.7%, and a less frequent A-A haplotype at 7.1%. This study underscores associations between CYP1A2 gene variants, particularly rs762551 (CYP1A2-163 C/A), and an increased susceptibility to BLCA. Haplotype analysis of 340 individuals reveals a predominant C-C haplotype at 38.2%, followed by a C-A haplotype at 54.7%, and a less frequent A-A haplotype at 7.1%. CONCLUSION: In conclusion, the - 163 C/A allele, C/A genotype of rs762551, and G/A genotype of rs2069514 emerge as potential genetic markers associated with elevated BLCA risk.	bladder